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Saliva
Saliva is a watery substance secreted by the salivary glands in and around the mouth. Human saliva is 99.5% water. The rest is composed of electrolytes enzymes, mucus, glycoproteins, and antibacterial components (e.g. IgA and lysozymes). Saliva is an essential part of the digestive process; it assists in starch and fat breakdown, aids swallowing protects teeth from decay, and prevents the dessication of the mucosal surfaces of the oral cavity. Functions Saliva has a wide variety of functions owing to the presence of many different chemical components within it. 'Lubrication' Saliva serves to lubricate the oral mucosa, protecting it from damaging friction and trauma during masitcation, swallowing, and speaking. Those who produce insufficient saliva (xerostomia) e.g. from disease or as a side effect of a drug, often experience mouth soreness and difficulty swallowing 'Digestion' The moistening of foodstuffs helps to create and swallow a bolus. Saliva contains amylase (ptyalin) which is capable of breaking down starches (complex sugars) into simpler sugars that can later be absorbed or further broken down by intestinal enzymes. It also contains a potent lipase which aids fat digestion. The salivary lipase is especially important in infancy as the pancreas - the main source of lipases - has not yet fully developed 'Antimicrobial action' Aside from saliva's mechanical cleansing of the oral cavity, it also contains immune specific (IgA) and non-specific (lysozyme, lactoferrin, myeloperoxidase) components which help to control the bacterial population of the mouth. They are essential in preventing the buildup of dental plaque and food residues, and in halting ascending salivary gland infections such as parotitis. 'Ion reservoir/buffer function' Saliva is supersaturated with a wide range of ions. They all play various roles in buffer systems that help to maintain the pH of the mouth at 6.2-7.4 in order to prevent the hard dental tissues from dissolving. Proteins within salivary secretions prevent the precipitation of these ions into solid salts. There are three buffering systems used to maintain healthy pH: The protein, phosphate, and bicarbonate systems. The protein system's role is minor due to the very small number of free, ionised groups in amino acids (most of the potential groups are being utilised in peptide bonds with other amino acids). The phosphate system relies on the secondary phosphate ion's (HPO42-) ability to bind an H+ ion (forming H2PO4-), however, there is unsufficient phosphate in unstimulated saliva for this to be a useful system. Therefore the main system, especially in stimulated saliva, is the bicarbonate buffering system, which is also heavily employed in blood. 'Role in taste' Saliva provides a liquid medium via which the chemicals in food that we taste can be carried to taste receptor cells on taste buds. Decreased saliva production (xerostomia) often causes dysgeusia. Contents Saliva's wide range of functions is due to the many constituents which comprise it. Its high water content facilitates the rest of its actions. 'Electrolytes' Salts and other ionisable compounds are secreted in the saliva to perform a variety of jobs. Saliva is supersaturated with phosphorus and calcium so that enamel is constantly exposed to repair processes. The bicarbonate (HCO-3) acts as a buffer in a similar fashion to the bicarbonate buffering system in blood. *Magnesium (barely present in plasma) - roles in enzyme activation *Phosphate (barely present in plasma) - works in conjunction with calcium to facilitate enamel repair *Sodium (lower conc. than in plasma) - responsible for some of the 'salty' taste amongst others *Chloride (lower conc. than in plasma) - responsible for some of the 'salty' taste *Calcium (similar conc. to plasma) - works in conjunction with phosphate to facilitate enamel repair *Bicarbonate (higher conc. than in plasma) - responsible for the main buffer system of saliva *Potassium (higher conc. than in plasma) - plays a role in the reabsorption of water and sodium in the mouth 'Mucus' Salivary mucus secretions largely consist of mucopolysaccharides (glycosaminoglycans) and assorted glycoproteins which have limited function besides some taste modulations (e.g. miraculin is a glycoprotein that causes sour foods to taste sweet). 'Antibacterial components' Saliva combats microbial attack with a few different mechanisms, for example: *Thiocyanate (SCN-) - made from cyanide and thiosulfate. Lactoperoxidase enzymes catalyse its reaction with hydrogen peroxide to form hypothiocyanite, a potent bactericidal agent, which works by oxidising sulfhydryls in the bacteria, preventing glucose transport and causing potassium leakage. Patients with cystic fibrosis release insufficient thiocyanate, thus providing a possible route for infection. *Hydrogen peroxide (H2O2) - a highly reactive oxidising compound that is a product of normal, aerobic respiration. Normally removed by catalase peroxidases. May act as a signal to WBCs to converge at a site to begin the healing process. *Immunoglobulin A (IgA) - found in all mucosal secretions in high quantities, and to a lesser extent in serum. More IgA is produced in mucosal linings than all other Ig types combined. It exists in 2 isoforms (IgA1 and IgA2), though IgA2 is predominant in secretions such as saliva. Can exist dimerically, joined by a 'secretory component' which confers protection from proteolytic enzymes. Works as any other antibody does; by binding to antigens on the surface of pathogens and marking them for destruction. 'Enzymes' A vast array of ezymes exists in saliva, but the main ones aid digestion, catalyse the breakdown of harmful substances, and help prevent a buildup of bacteria. 'Digestive' *Alpha-amylase (ptyalin) - an enzyme that catalyses the breakdown of starches into simpler sugars (maltose, amongst others). This is the reason that high-starch foods like bread and rice taste slightly sweet if not swallowed; they are already being digested. Produced by the salivary glands and pancreas to hydrolyse starches to di- and trisaccharides, before it is converted to glucose by other enzymes. *Lingual lipase - an enzyme which utilises the catalytic triad of aspartate, histidine, and serine to hydrolyse triglycerides to their constituent molecules (mainly diglycerides). It has an optimum pH of 4.5-5.4 and so is most active after being swallowed. Essential as long-chain triglycerides cannot be absorbed by the intestines. *Kallikrein - a subgroup of serine proteases that perform a wide range of functions throughout the body. Some activate bradykinin to regulate blood pressure, others play a role in neuroplasticity, and more. 'Antibacterial' Aside from the straight digestive enzymes, there are also some antibacterial enzmes: *Lactoperoxidase - catalyses the oxidation of iodine and bromine by hydrogen peroxide, as well as the conversion of thiocyanate to hypothiocyanite. *Lysozymes - a group of glycosidic hydrolases which damage the links between sugars in peptidoglycans, a building block of bacterial cell membranes. *Lactoferrin - a protein that serves to sequester free iron, thus hoarding one of the essential components for bacterial reproduction. It also binds to lipopolysaccharide receptors on bacterial cell membranes, oxidising them to produce peroxides, which causes cell death by altering the membrane permeability. Production and salivation 'Stimulation of salivation' Saliva is produced in the salivary glands, of which there are three pairs: Sub-lingual, sub-mandibular, and parotid. It's secretion is stimulated by both the sympathetic and the parasympathetic systems. Sympathetic activation causes production of a thicker saliva primarily for respiration, whilst parasypathetic activation results in a more watery secretion primarily for digestion. The salivatory nuclei are located at the pontine-medulla junction, and communicate with the appetite, visual, and taste and tactile centres of the brain, as well as with the stomach which can relay info regarding irritation that can be resolved by an increase in saliva. Parasympathetic stimulation causes the release of acetylcholine onto acinar cells of the salivary glands, where it binds to M3 receptors to cause an increase in intracellular calcium (via the IP3/DAG cascade). This causes ACh-containing vesicles to fuse with the cell membrane and release their contents. ACh also causes kallikrein release from the salivary glands, which activates bradykinin, which in turn causes capillary dilation in the salivary gland. The increased blood flow allows for more saliva production. Secondary to this, substance P is also released, which can bind to tachykinin NK-1 receptors, increase intracellular calcium, and result in even more saliva production. Sympathetic stumulation causes noradrenaline release, which binds to either α- and β-andrenergic recptors. Alpha binding causes more fluid secretion, whereas beta binding causes more protein secretion. Initially noradrenaline release decreases blood flow to the salivary glands, but local vasodilator action quickly overrides this. Sialagogues are drugs that artificially stimulate saliva production, whereas antisialagogues inhibit it. 'Salivary glands' There are 3 pairs of salivary glands; sub-lingual, sub-mandibular, and parotid. They are all exocrine glands; meaning their secretions do not go directly to the bloodstream, but instead to various cavities and organs via ducts. 'Histology' The glands are divided into lobules. Blood vessels and nerves enter through the hilum before branching out into the different lobules. Acini (singular: Acinus), are groups of secretory cells found in each lobule at the terminal portion of glands just before the ductal system. They consist of a single layer of cuboidal epithelial cells around a lumen where they deposit saliva. There are three forms of acini, named depending on the type of secretion they are responsible for; Serous, mucoserous, and mucous. Lumina in salivary glands form intercalated ducts, which join to form striated ducts, which in turn join to ducts from other lobules via interlobar ducts. Saliva is then secreted into the oral cavity. The majority of salivary components are disabled by the highly acidic stomach environment, although some enzymes (e.g. lipases) are actually activated. 'Anatomy - the different glands' The parotid glands are the largest salivary glands. They are wrapped around the ramus of the mandible and produce mostly serous secretions which they release via the parotid (Stensen) duct. It is contained within a fibrous capsule, and inflammatory infections (e.g. parotitis from mumps) can cause swelling and pain because of this. Innervated by CN IX. The sub-mandibular glands are located below the floor of the mouth and produce the majority (~60%) of the total secretions. Separated into deep and superficial lobes between which runs the mylohyoid muscle. They secrete saliva via the submandibular (Wharton) duct into the oral cavity via the sublingual caruncles on either side of the lignual frenulum. The saliva produced here is primarily mucous in nature, containing mucin to help facilitate bolus formation. Innervated by CN VII. The sub-lingual glands are mucoserous glands (although they produce mostly mucous secretions), located beneath the tongue. They release only about 5% of the total volume of saliva, and lack intercalated or striated ducts, instead secreting directly into the oral cavity via 8-20 excretory ducts. Innervated by CN VII. Von Ebners glands are tiny glands found in the troughs surrounding circumvillate papillae of the tongue. They release a purely serous secretion directly into the oral cavity that begins lipid hydrolysis. Innervated by CN IX. There are also 800-1000 minor salivary glands throughout the oral cavity, located within the submucosa. Their secretions are largely mucous in nature and they serve to keep the entire oral cavity constantly covered in saliva. They are innervated by CN VII.